Rasagiline, a Suicide Inhibitor of Monoamine Oxidases, Binds Reversibly to α-Synuclein
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Rasagiline (N-propargyl-1-R-aminoindan) and selegiline (1-deprenyl) are MAO-B inhibitors which are used in the treatment of Parkinson's disease. The binding of rasagiline, selegiline, and their metabolites including 1-aminoindan, 2-aminoindan, and methamphetamine to α-synuclein was investigated by nanopore analysis and isothermal titration calorimetry. Blockade current histograms of α-synuclein alone give a peak at -86 pA which is due to translocation of the protein through the pore. In the presence of rasagiline and R-1-aminoindan, this peak shifts to about -80 pA. In the presence of selegiline and R-methamphetamine, the number of events at -86 pA is reduced and there is a higher proportion of bumping events at about -25 pA which are due to a more compact conformation. Rasagiline can also bind to sites in both the N- and C-terminal regions of α-synuclein. The binding constants of rasagiline and selegiline were estimated by isothermal titration calorimetry to be about 5 × 10(5) and <10(4) M(-1), respectively. A model is presented in which both rasagiline and R-1-aminoindan bind to α-synuclein, forming a loop structure which is less likely to aggregate or form fibrils. In contrast, selegiline binds and forms a more compact structure similar to that formed by methamphetamine.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it